Cell-permeable esters of diazeniumdiolate-based nitric oxide prodrugs.
Although O(2)-(2,4-dinitrophenyl) derivatives of diazeniumdiolate-based nitric oxide (NO) prodrugs bearing a free carboxylic acid group were activated by glutathione to release NO, these compounds were poor sources of intracellular NO and showed diminished antiproliferative activity against human leukemia HL-60 cells. The carboxylic acid esters of these prodrugs, however, were found to be superior sources of intracellular NO and potent inhibitors of HL-60 cell proliferation.
Chakrapani
Harinath
H
Chemistry Section, Laboratory of Comparative Carcinogenesis, National Cancer Institute at Frederick, Frederick, Maryland 21702, USA. chakrah@ncifcrf.gov
Maciag
Anna E
AE
Citro
Michael L
ML
Keefer
Larry K
LK
Saavedra
Joseph E
JE
D000818:Animals; D001391:Azo Compounds / Q000737:chemistry*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D042541:Intracellular Space / Q000378:metabolism; D009569:Nitric Oxide / Q000737:chemistry* / Q000378:metabolism* / Q000494:pharmacology; D010539:Permeability; D011355:Prodrugs / Q000737:chemistry* / Q000378:metabolism* / Q000494:pharmacology; D051381:Rats
D001391:Azo Compounds; D011355:Prodrugs; C452539:diazeniumdiolate; D009569:Nitric Oxide